We propose to investigate the basic mechanism of action of selected pancreatic carcinogens, in order to determine the relative roles of their selective uptake, metabolism, cellular distribution, target organ specificity, and excretion in bile and pancreatic juice, in the experimental induction of exocrine pancreatic cancer in guinea pigs. In vivo metabolic studies will be undertaken with the following pancreatic carcinogens: di-n-propyl nitrosamine (DPN) and/or di-isopropanol nitrosamine (DIPN), 4-nitroquinoline-1-oxide (NQO) and/or 4-hydroxyaminquinoline-1-oxide (HAQO), and benzo(a)pyrene (BP); following their administration, blood, urine, pancreatic juice, bile, pancreas, and liver will be sequentially analyzed for the parent compounds and their metabolites. In situ localization will be determined autoradiographically and histochemically. For comparative purposes, similar studies on in vivo metabolism will be undertaken in animals following pre-treatment with the known inducers of metabolism, such as phenobarbital and 3-methylcholanthrene.